1. Field of the Invention
The invention relates to a multilayer preparation in the form of films of hydrophilic polymers which is suitable for delivering the substances present therein to the surroundings within a short time. The invention relates in particular to preparations of the type mentioned, whose layers contain pharmacologically active substances. The invention further relates to a process for producing such preparations, and to the use thereof.
2. Description of the Related Art
In systems for delivering active ingredients, in particular in pharmaceutical forms, it is necessary in relation to certain areas of use for a relatively large amount of a pharmacologically active substance to be released in the human or animal body within a short time. This can be achieved, for example, by aiming in the formulation of the pharmaceutical form at a surface area which is as large as possible by comparison with the volume. In accordance with the laws of diffusion, this increases the rate of delivery of the constituents to the surroundings.
However, there are limits to increasing the surface area because the substance-delivering composition must, on the other hand, also be as compact as possible in order to confer adequate strength on the system and make handling easily possible. Thus, for example, the area of oral dosage forms cannot be increased indefinitely.
The requirement for rapid release of active ingredient with, at the same time, compactness is met by dosage forms in the form of films which contain the active ingredients in dissolved, emulsified or suspended form. Because the dimension in the direction of the thickness of the film is relatively small, the diffusion pathways are short and thus the times required for dissolution are also short, so that high rates of release can be achieved.
It is known to produce such films from hydrophilic polymers as film-forming agent, where appropriate with the addition of auxiliaries to adjust the physicochemical parameters of the film, the chemical stability and/or the taste. Such films can be obtained by producing a solution which contains the polymer matrix in a hydrophilic solvent, usually water. This solution is mixed with active ingredients and auxiliaries and coated onto a processing sheet made of plastic or metal. The solvent is removed by subsequent drying, and the polymer matrix remains behind as film. However, only a certain maximum film thickness can be achieved with this process, the kinetics of drying representing the limiting factor. The possible rate of coating particularly for aqueous systems is, owing to the relatively high heat of vaporization, relatively low in coupled coating and drying machines, so that there are corresponding limits on the film thickness which can be achieved in this way.
It is true that such relatively thin films have the advantage that they are relatively rapidly dissolved in the body and thus bring about rapid release of active ingredient. However, since the mode of production limits the film thickness, this also results in a restriction concerning the loading with active ingredients. For this reason, monolayer films are associated with the disadvantage that the maximum possible total dose is low.
If combination products having said properties are required, a further possible problem with these thin films is the chemical incompatibility of two or more active ingredients, or else other constituents, for example, odorizers.
It is true that it is possible in principle to achieve multilayer coating by applying to an active ingredient-containing film which is already present a plurality of further layers of the same film-forming solution successively, with a drying being carried out after each application. However, in practice, this leads to the layers which are already present in each case being attacked or dissolved by the solvents in the polymer solution which is applied subsequently. This may on the one hand interfere with the production process, and on the other hand it prevents the formation of genuine multilayer systems in which the individual layers are separate from one another. It is true that dissolution of the layer produced first could be prevented by inducing certain crystallization processes therein. However, this would be associated with an unwanted reduction in the solubility of the film layers in aqueous solutions, which in turn has an adverse effect on the release of active ingredient.